Germicidal compositions containing halogenated anilides of thiophene carboxylic acids



United States Patent 3,243,342 GERMICIDAL COMPOSITIONS CONTAINING HALOGENATED ANILIDES OF THIOPHENE CARBOXYLIC ACIDS Herbert C. Stecker, Ho-Ho-Kus, NJ. No Drawing. Filed Feb. 24, 1964, Ser. No. 347,007 '7 Claims. (Cl. 16733) This application is a-continuation-in-pa1t of copending application Serial No. 328,105, filed on December 4, 1963, by Herbert C. Stecker, now abandoned.

This invention deals with germicidal compositions containing halogenated anilides of thiophene carboxylic acids; More specifically, it relates to germicidal compositions containing compounds having the following generic formula:

A H Q -t l wherein X is a halogen atom selected from the class consisting of chlorine, bromine, and iodine, A is an atom selected from the class consisting of oxygen and sulfur, a is a numeral from 0 to 2, and b is a numeral from 1 to 3.

Condensation products of some carboxylic acids and halogenated anilines have been known to possess some dyeing characteristics, but none of .the compounds have been considered to have suificientgermicidal potency to justify commercial consideration.

It has now been discovered that the amide condensation products of thiophene carbox-ylic acids and thio acids with halogenated anilines show high germicidal potency.

The germicidal compounds of the present invention may be prepared in accordance with the method outlined by Hopper, MacGregor and Wilson in the January 1941 issue of the Journal of the Society of Dyers and Colourists, page 6. Further details for the preparation of the compounds described herein may be found in the article by Hopper, MacGregor and Wilson, Journal Society of Dyers and Colourists, 1939, 55, 450. The procedure for preparing arylamides of 2-hydroxy-3-naphthoic acid is followed, with the exception that the corresponding acid and amine of the desired compound, in the molal quantities required, are substituted. For example, to prepare compound No. 1 of Table I herein, one would use 2-thiophene carboxylic acid and p-chloroaniline. Table I lists a number of compounds prepared in accordance with the present invention, and gives their germicidal effectiveness against S. aureus in agar test plates, as millimeters of zone of inhibition. The tests were carried out in triplicate as follows:

Bacteriological tests were performed against Staphylococcus aureus with a 24-hour culture at 37 C. Each of the compounds in Table I was incorporated in soap of Ivory brand (a neutral white high grade toilet soap consisting of a mixture of 80% sodium soap and 20% potassium soap produced from a 70% tallow and 30% coconut oil glyceride blend, in accordance with US. Patent 2,295,594), in 1% by weight concentration of soap and 0.1% of the compound listed. Cotton disks of mm. diameter were steeped in this mixture, thoroughly rinsed, dried, and applied to seeded agar in Petri dishes, and the zones of inhibition were read after 24 hours, the average data being reported in Table I.

These compounds of the present invention are useful in compositions comprising a germicidally inert material, i.e., relatively speaking. For example, some soaps and detergents possess a bactericidal action, but such action, relative to those of the compounds of the present invention, is weak and of little effect in comparison with the overall germicidal activity of the composition. In such Ice compositions, the compounds of the present invention maybe employedinconcentrations as low as 10 ppm, although, from a practical point of view, it is desirable to use as much as 50 ppm, or 0.001% by weight, or 0.01%, and as much as 0.1%, or more. The term germicidal: activity includes inhibiting and killing action against bacteria, fungi and similar organisms.

Particularly useful compositions of. the. present. invention are those comprising soaps and detergents, and especially toilet soaps or cosmetic detergents in which the compounds of the present invention may be employed in concentrations of 0.1% to 0.5% by'weight, or even as much as 1% or more. The term detergent employed herein will be used toinclude all synthetic and natural cleansing compositions, including cationic detergents, such as dimethyl stearamido-propyl-2hydroxy-ammonium dihydrogen phosphate, anionic detergents such as commercial soaps, e.g., alkali metal soaps of hydrolyzed natural or synthetic glycerides of fatty and similar organic acids, e.g., sodium and potassium stearates or oleates, ampholytic detergents, such as sarcosine, non-ionic detergents such as polyoxypropylene polyoxyethylene condensates, natural detergents, such as starches, vegetable gums, and the like, and mixtures thereof. The term soap employed herein is used in its popular or ordinary meaning, i.e., a cleansing composition prepared from an alkali metal compound such as potassium or sodium hydroxide and a fat or fatty acid, both saturated and unsaturated.

One valuable use of the compounds of the present invention is the use thereof to sanitize fibrous material such as cotton gauze, dressings, textiles, paper pulp, and the like. They also serve as antiseptic agents when incorporated in plastic or rubber compositions, prior to molding into articles of commerce, such as baby rattles, gloves, food wrappers and the like.

T able] Compound Zone of No. Formula Inhibition,

0 H S II I 1 Cl 2.0

s H 5 I1 I 2 N I 2.0

Cl 0 H S I] l 3 GN- I 3.0 Cl

01 l o H l I s H 4 Br O-N- 3.0

5 H S ll 1 5 o1 C-N I 3.0

s H S I] I 6 Br -C-N Br 3.0

1 Br Br 3 Table I--Continued A study of Table I will reveal that the germicidal potency of the compounds of the present invention do not appear to be increased substantially by the addition of extra halogen atoms to the nuclei. This is apparent when Compound No. 3 is compared with No. 4. It therefore appears that thehigh germicidal power of the compounds of the present invention is inherent irrthe 2 structural arrangement of the molecules, rather thanto the halogen substituents.

Iclaim:

1. A method of obtaining germicidal activity against Staphylococcus aureus and other bacteria, fungi ,and similar micro-organisms, comprising, i

contacting said micro-organisms with a germicidally effective concentration of at least one compound having the general formula:

t e- C? where 35 X is chlorine, bromine or iodine, A is oxygen or sulfur, a is a numeral from to 2, and b is a numeral from 1 to 3. 2. A method according to claim 1 in which the compound has the formula:

I 4. A method according to claim 1 in which the compound has the formula: 1

13r 5. A method according to claim 1 in which the compound has the formula:

sI H

Br- Br 6. A method according to claim 1 in which the compound has the formula:

go h-@411 w Xb where X is chlorine, bromine or iodine, A is oxygen or sulfur,

a is a numeral from 0 to 2, and

b is a numeral from 1 to 3.

References Cited by the Examiner Chem. Abstracts 46, 8772d 1952).

Chem. Abstracts 55, 17985d (1961).

"Chem. Abstracts 57, page 1066s, July-December 1962.

Chem. Abstracts 58, page 955s, January-June 1963.

Chem. pages 5398s-5399s.

Chem. Abstracts 6th Collective Index, 19574961,

page 5043s.

Hopper, I.V., et al.: The Preparation of Certain Thiolcarboxylic Acids and Their'Arylmides, J. Soc. Dyers Colourists 57,"pp. 69'(1941); abstracted in Chem. Ab-

stracts 35, 2484(8)-2485(2) (1941).

LEWIS GOTTS, PrimaryExaminer.

S, K. ROSE, Assistant Examiner,

Abstracts Sth Collective Index, 1947-1956,; 

1. A METHOD OF OBTAINING GERMICIDAL ACTIVITY AGAINST STAPHYLOCOCCUS AUREUS AND OTHER BACTERIA, FUNGI AND SIMILAR MICRO-ORGANISMS, COMPRISING, CONTACTING SAID MICRO-ORGANISMS WITH A GERMICIDALLY EFFECTIVE CONCENTRATION OF AT LEAST ONE COMPOUND HAVING THE GENERAL FORMULA: 